Abstract
Liver and kidney damage associated with polytrauma, endotoxic shock/sepsis, and organ transplantation, are among the leading causes of the multiple organ failure. Development of novel sensitive biomarkers that detect early stages of liver and kidney injury is vital for the effective diagnostics and treatment of these life-threatening conditions. Previously, we identified several hepatic proteins, including Argininosuccinate Synthase (ASS) and sulfotransferases which were degraded in the liver and rapidly released into circulation during Ischemia/Reperfusion (I/R) injury. Here we compared sensitivity and specificity of the newly developed sandwich ELISA assays for ASS and the sulfotransferase isoform SULT2A1 with the standard clinical liver and kidney tests Alanine Aminotransferase (ALT) and Aspartate Transaminase (AST) in various pre-clinical models of acute injury. Our data suggest that ASS and SULT2A1 have superior characteristics for liver and kidney health assessment in endotoxemia, Ischemia/Reperfusion (I/R), chemical and drug-induced liver injury and may be of high potential value for clinical applications.
Highlights
Liver and kidney damage and failure due to various forms of intoxication and abdominal injury are significant sources of overall morbidity and mortality in the US and worldwide
Our data suggest that Argininosuccinate Synthase (ASS) and SULT2A1 have superior characteristics for liver and kidney health assessment in endotoxemia, Ischemia/Reperfusion (I/R), chemical and drug-induced liver and kidney injury and may be of high potential value for clinical applications
To assess quantitatively the levels of endogenous ASS and in rat serum after LPS treatment alone and in combination with the liver injury priming agent D-Galactosamine (D-Gal) we used the ELISA assay developed at Banyan Biomarkers [9]
Summary
Liver and kidney damage and failure due to various forms of intoxication and abdominal injury are significant sources of overall morbidity and mortality in the US and worldwide. The increase of ALT and AST in blood has been used in clinical practice for a long time for diagnostics of viral hepatitis of all types and alcoholic/toxic hepatitis, and monitoring of treatment. Several other enzymes such as isocitrate dehydrogenase [1] and anti-oxidative enzyme GlutathioneS-Transferase (GST) [2] were shown as potential markers for viral hepatitis injury. In the current study we compared sensitivity and specificity of the newly developed ELISA assays for ASS and the SULT2A1 with standard clinical liver and kidney function assays for Alanine Aminotransferase (ALT) and Aspartate Transaminase (AST) in various pre-clinical models of acute toxicity. Our data suggest that ASS and SULT2A1 have superior characteristics for liver and kidney health assessment in endotoxemia, Ischemia/Reperfusion (I/R), chemical and drug-induced liver and kidney injury and may be of high potential value for clinical applications
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